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AZD6244 (Selumetinib)

现货
Catalog No.
A8207
MEK抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 550.00
现货
100mg
¥ 800.00
现货
500mg
¥ 2,700.00
现货

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Background

AZD6244 is a highly potent and selective inhibitor of MEK1/2 with IC50 value of 14.1nM against MEK1 [1].

AZD6244 is a second generation MEK1/2 inhibitor. In the radioactive assay, AZD6244 shows potent inhibition against the purified MEK1without the competition with ATP. Besides, it is a selective inhibitor since it has no obvious inhibition against other tyrosine kinases including MKK6, EGFR, ErbB2 and B-Raf et al. In the cellular assay, AZD6244 inhibits the phosphorylation of ERK1/2 which are the direct substrates of MEK1/2. The IC50 value is 10.3nM. It also inhibits the EGF-induced phosphorylation of ERK1/2 but not ERK5 in A431 cells. Since MEK is important in cell proliferation, the block of MEK1/2 caused by AZD6244 leads to a growth inhibition in the cell lines containing activating B-Raf and Ras mutations with IC50 values ranging from 59 to 473nM. Furthermore, the administration of AZD6244 can significantly inhibit tumor growth both in the HT-29 xenograft model and the BxPC3 pancreatic tumor xenograft model [1].

References:
[1] Yeh TC, Marsh V, Bernat BA, Ballard J, Colwell H, Evans RJ, Parry J, Smith D, Brandhuber BJ, Gross S, Marlow A, Hurley B, Lyssikatos J, Lee PA, Winkler JD, Koch K, Wallace E. Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor. Clin Cancer Res. 2007 Mar 1;13(5):1576-83.

文献引用

1. Bunda S, Heir P, et al. "CIC protein instability contributes to tumorigenesis in glioblastoma." Nat Commun. 2019 Feb 8;10(1):661. PMID:30737375
2. Khan IA, Yoo BH, et al. "Mek activity is required for ErbB2 expression in breast cancer cells detached from the extracellular matrix." Oncotarget. 2017 Oct 31;8(62):105383-105396. PMID:29285258
3. Sieber J, Wieder N, et al. "GDC-0879, a BRAF(V600E) Inhibitor, Protects Kidney Podocytes from Death." Cell Chem Biol. 2017 Dec 6. PMID:29249695

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt457.69
Cas No.606143-52-6
FormulaC17H15BrClFN4O3
Solubility≥22.9mg/mL in DMSO, <2.36 mg/mL in EtOH, <2.28 mg/mL in H2O
Chemical Name6-(4-bromo-2-chloroanilino)-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamide
SDFDownload SDF
Canonical SMILESCN1C=NC2=C1C=C(C(=C2F)NC3=C(C=C(C=C3)Br)Cl)C(=O)NOCCO
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验[1]:

细胞系

1205Lu细胞(BRAFV600E)

溶解方法

在DMSO中的溶解度>10 mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

3 μM;24小时

应用

AZD6244诱导可逆的G1期细胞周期停滞,从而抑制细胞生长。贴壁1205Lu细胞用DMSO或3 μM AZD6244处理24 h或处理24 h后去除药物再培养24 h,细胞进入G1期细胞周期停滞,但当药物去除后,其重新进入S期。

动物实验[2]:

动物模型

植入HT-29人结肠癌的裸鼠

剂量

10、25、50或100 mg/kg,2次/天,21天;口服给药

应用

AZD6244在所有测试剂量下有效抑制肿瘤生长。两个最高剂量组到达肿瘤生长终点的时间是36天,而对照组是18天。在10 mg/kg的低剂量组和100 mg/kg的高剂量组,AZD6244给药11天后分别抑制55%和70%的肿瘤生长。停止给药后观察到肿瘤生长的恢复。在100 mg/kg剂量组,肿瘤的再生长显著延迟。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1] Haass N K, Sproesser K, Nguyen T K, et al. The mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor AZD6244 (ARRY-142886) induces growth arrest in melanoma cells and tumor regression when combined with docetaxel. Clinical Cancer Research, 2008, 14(1): 230-239.

[2] Yeh T C, Marsh V, Bernat B A, et al. Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor. Clinical Cancer Research, 2007, 13(5): 1576-1583.

生物活性

描述 Selumetinib (AZD6244)是一种有效的和高选择性的MEK1抑制剂,IC50值为14 nM。
靶点 MEK1          
IC50 14 nM          

质量控制

化学结构

AZD6244 (Selumetinib)

相关生物数据

AZD6244 (Selumetinib)

相关生物数据

AZD6244 (Selumetinib)

相关生物数据

AZD6244 (Selumetinib)

相关生物数据

AZD6244 (Selumetinib)

相关生物数据

AZD6244 (Selumetinib)